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2.  Aspiration dynamics in structured population acts as if in a well-mixed one 
Scientific Reports  2015;5:8014.
Understanding the evolution of human interactive behaviors is important. Recent experimental results suggest that human cooperation in spatial structured population is not enhanced as predicted in previous works, when payoff-dependent imitation updating rules are used. This constraint opens up an avenue to shed light on how humans update their strategies in real life. Studies via simulations show that, instead of comparison rules, self-evaluation driven updating rules may explain why spatial structure does not alter the evolutionary outcome. Though inspiring, there is a lack of theoretical result to show the existence of such evolutionary updating rule. Here we study the aspiration dynamics, and show that it does not alter the evolutionary outcome in various population structures. Under weak selection, by analytical approximation, we find that the favored strategy in regular graphs is invariant. Further, we show that this is because the criterion under which a strategy is favored is the same as that of a well-mixed population. By simulation, we show that this holds for random networks. Although how humans update their strategies is an open question to be studied, our results provide a theoretical foundation of the updating rules that may capture the real human updating rules.
doi:10.1038/srep08014
PMCID: PMC4306144  PMID: 25619664
3.  Transcriptional Consequence and Impaired Gametogenesis with High-Grade Aneuploidy in Arabidopsis thaliana 
PLoS ONE  2014;9(12):e114617.
Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.
doi:10.1371/journal.pone.0114617
PMCID: PMC4267805  PMID: 25514186
4.  Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge 
Background
Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection.
Methodology/Principal Findings
Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7.
Conclusions/Significance
The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis.
Author Summary
Leptospirosis is the most widespread bacterial infection transmitted from animals to man. Humans are exposed to infection when host animals that harbor the bacteria in their kidneys shed them in their urine. Human infections, caused by the bacterium Leptospira interrogans, frequently result in a life-threatening illness characterized by liver and kidney failure. In the hamster model of leptospirosis, signs of hepatic and renal dysfunction developed on days 6 and 7, respectively, after intradermal and subcutaneous inoculation of L. interrogans. Renal dysfunction was preceded by the development of inflammatory changes and the appearance of large numbers of leptospires in the kidney on day 5. On day 6, animals began to lose weight, became dehydrated, and had elevated numbers of neutrophils circulating in their bloodstream. Importantly, animals inoculated intradermally had lower numbers of bacteria in their liver and kidneys on day 6 than animals inoculated subcutaneously and lower weight loss and circulating neutrophil levels on day 7. These studies show that the hamster model of leptospirosis is similar to human infection and indicate that the route of infection has significant effects on the course of the illness.
doi:10.1371/journal.pntd.0003307
PMCID: PMC4239013  PMID: 25411782
5.  Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms 
World Journal of Gastroenterology : WJG  2014;20(41):15335-15342.
AIM: To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle.
METHODS: Isolated strips of gastrointestinal smooth muscle from Spraque-Dawley rats were suspended in organ baths containing Kreb’s solution, and the contractility of smooth muscles was measured before and after incubation with resveratrol and genistein, and the related mechanisms were studied by co-incubation with various inhibitors.
RESULTS: Resveratrol and genistein dose-dependently decreased the resting tension, and also reduced the mean contractile amplitude of gastrointestinal smooth muscle. Estrogen receptor blockades (ICI 182780 and tamoxifen) failed to alter the inhibitory effects induced by resveratrol and genistein. However, their effects were attenuated by inhibitions of α-adrenergic receptor (phentolamine), nitric oxide synthase (levorotatory-NG-nitroarginine), ATP-sensitive potassium channels (glibenclamide), and cyclic adenosine monophosphate (SQ22536). In high K+/Ca2+-free Kreb’s solution containing 0.01 mmol/L egtazic acid, resveratrol and genistein reduced the contractile responses of CaCl2, and shifted its cumulative concentration-response curves rightward.
CONCLUSION: Resveratrol and genistein relax gastrointestinal smooth muscle via α-adrenergic receptors, nitric oxide and cyclic adenosine monophosphate pathways, ATP-sensitive potassium channels, and inhibition of L-type Ca2+ channels.
doi:10.3748/wjg.v20.i41.15335
PMCID: PMC4223267  PMID: 25386082
Ca2+ channel; Gastrointestinal; Motility; Phytoestrogen; Smooth muscle
6.  Identification of miRNAs involved in pear fruit development and quality 
BMC Genomics  2014;15(1):953.
Background
MicroRNAs (miRNAs) are a class of small, endogenous RNAs that take part in regulating genes through mediating gene expressions at the post-transcriptional level in plants. Previous studies have reported miRNA identification in various plants ranging from model plants to perennial fruit trees. However, the role of miRNAs in pear (Pyrus bretschneideri) fruit development is not clear. Here, we investigated the miRNA profiles of pear fruits from different time stages during development with Illumina HiSeq 2000 platform and bioinformatics analysis. Quantitative real-time PCR was used to validate the expression levels of miRNAs.
Results
Both conserved and species-specific miRNAs in pear have been identified in this study. Total reads, ranging from 19,030,925 to 25,576,773, were obtained from six small RNA libraries constructed for different stages of fruit development after flowering. Comparative profiling showed that an average of 90 miRNAs was expressed with significant differences between various developmental stages. KEGG pathway analysis on 2,216 target genes of 188 known miRNAs and 1,127 target genes of 184 novel miRNAs showed that miRNAs are widely involved in the regulation of fruit development. Among these, a total of eleven miRNAs putatively participate in the pathway of lignin biosynthesis, nine miRNAs were identified to take part in sugar and acid metabolism, and MiR160 was identified to regulate auxin response factor.
Conclusion
Comparative analysis of miRNAomes during pear fruit development is presented, and miRNAs were proved to be widely involved in the regulation of fruit development and formation of fruit quality, for example through lignin synthesis, sugar and acid metabolism, and hormone signaling. Combined with computational analysis and experimental confirmation, the research contributes valuable information for further functional research of microRNA in fruit development for pear and other species.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-953) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-953
PMCID: PMC4233070  PMID: 25366381
Pear; Fruit development; High-throughput sequencing; miRNA; Lignin synthesis; Sugar and acid
7.  TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells 
Molecular Medicine Reports  2014;11(2):982-988.
Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes-associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK-N-BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK-N-BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK-N-SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial-mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF-β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.
doi:10.3892/mmr.2014.2818
PMCID: PMC4262480  PMID: 25354978
epithelial-to-mesenchymal transition; neuroblastoma; TAZ; connective tissue growth factor; transforming growth factor-β signaling
8.  A Comparative Study of Fast-Track Verus Conventional Surgery in Patients Undergoing Laparoscopic Radical Cystectomy and Ileal Conduit Diversion: Chinese Experience 
Scientific Reports  2014;4:6820.
Fast-track surgery (FTS), which combines various techniques with evidence-based adjustments, is aimed to reduce postoperative morbidity, attenuate surgical stress response, thereby accelerating recovery and shorting length of stay. To further investigate the effectiveness of fast-track surgery, we compared the short-term outcomes of laparoscopic radical cystectomy and ileal conduit diversion for Chinese bladder cancer patients with FTS or with CS in our hospital. Patients with bladder cancer were included and divided into two consecutive groups: CS group and FTS group. Duration to first flatus and regular diet, postoperative hospital days, hospital expense, incidence of complications and postoperative surgical stress response were compared. There was no significant difference between the two groups in age, sex, BMI and postoperative TNM classification. Compared with the CS group, the FTS group had significantly shorter duration to first flatus, time to regular diet, postoperative hospital days and hospital expense, less complications, lower white blood count (WBC) and serum of C-reactive protein (CRP) on postoperative day 5 and 7. Our study indicates that FTS program is safe and efficacious for Chinese patients undergoing laparoscopic radical cystectomy and ileal conduit diversion. It can accelerate recovery, reduce stress action, shorten postoperative hospitals days and reduce hospital expenses.
doi:10.1038/srep06820
PMCID: PMC4212226  PMID: 25352195
9.  Quantitative Trait Loci for Mercury Accumulation in Maize (Zea mays L.) Identified Using a RIL Population 
PLoS ONE  2014;9(9):e107243.
To investigate the genetic mechanism of mercury accumulation in maize (Zea mays L.), a population of 194 recombinant inbred lines derived from an elite hybrid Yuyu 22, was used to identify quantitative trait loci (QTLs) for mercury accumulation at two locations. The results showed that the average Hg concentration in the different tissues of maize followed the order: leaves > bracts > stems > axis > kernels. Twenty-three QTLs for mercury accumulation in five tissues were detected on chromosomes 1, 4, 7, 8, 9 and 10, which explained 6.44% to 26.60% of the phenotype variance. The QTLs included five QTLs for Hg concentration in kernels, three QTLs for Hg concentration in the axis, six QTLs for Hg concentration in stems, four QTLs for Hg concentration in bracts and five QTLs for Hg concentration in leaves. Interestingly, three QTLs, qKHC9a, qKHC9b, and qBHC9 were in linkage with two QTLs for drought tolerance. In addition, qLHC1 was in linkage with two QTLs for arsenic accumulation. The study demonstrated the concentration of Hg in Hg-contaminated paddy soil could be reduced, and maize production maintained simultaneously by selecting and breeding maize Hg pollution-safe cultivars (PSCs).
doi:10.1371/journal.pone.0107243
PMCID: PMC4161392  PMID: 25210737
10.  Application of piezoelectric nanogenerator in medicine: bio-experiment and theoretical exploration 
Journal of Thoracic Disease  2014;6(9):1300-1306.
Background
A large number of wearable and implantable electronic medical devices are widely used in clinic and playing an increasingly important role in diagnosis and treatment, but the limited battery capacity restricts their service life and function expansion. Piezoelectric nanogenerators can convert mechanical energy into electrical energy. Our experiment tries to find out if the piezoelectric nanogenerator fixed to the surface of the heart can convert the natural contractions and relaxations of the heart into stable electric energy for electronic medical devices such as pacemakers.
Methods
We used Chinese miniature pig and prepared with standard open chest procedure. Then we fixed two opposite edges of the rectangular nanogenerator at the following three positions of the heart respectively to detect the electric voltage output: Position A, right ventricular surface, near the atrioventricular groove, parallel to the long axis of the heart; Position B, right ventricular surface, parallel to the atrioventricular groove; and Position C, left ventricular surface, near cardiac apex, parallel to the left anterior descending branch. Then we selected the place which has the highest voltage output to fix both ends of the nanogenerator and closed the chest of pig. We recorded the voltage output of nanogenerator under closed chest condition (natural condition) and compared the result with open chest condition. Finally we used Dopamine (positive inotropic agents) and Esmolol (negative inotropic agents) respectively to detect the relation between voltage output of nanogenerator and myocardial contractility.
Results
With its both ends fixed on the surface of the heart, the piezoelectric nanogenerator produced stable voltage output from the mechanical contractions of the heart. Piezoelectric nanogenerator which was fixed at Position A produced the highest voltage output (3.1 V), compared with those fixed at Position B or Position C. The voltage is enough for the pacemaker’s operation. The voltage output of piezoelectric nanogenerator at the natural condition (closed chest) was the same as the open chest condition and made a light emitting diode (LED) light continue to shine, which further confirmed its clinical application value. The voltage output of piezoelectric nanogenerator is positively correlated with the myocardial contractile force. The voltage output increased after we used positive inotropic agents and decreased after we used negative inotropic agents.
Conclusions
Piezoelectric nanogenerators can convert the kinetic energy of the heart during the contractions and relaxations of the muscles to electric energy. The output voltage was stable in three positions on the surface of the heart. The highest voltage appeared on the surface of right ventricle, near atrioventricular groove, parallel to the long axis direction of the heart, which can be the potential new energy source for pacemakers. Piezoelectric nanogenerator can be used as cardiac function monitor in the future for its voltage output is positively correlated with myocardial contractile force.
doi:10.3978/j.issn.2072-1439.2014.09.03
PMCID: PMC4178096  PMID: 25276373
Implantable medical electronic device; wearable medical electronic device; piezoelectric nanogenerator; body mechanical energy; biomechanical energy harvester; new power source
11.  Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions 
There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance. Immunologic tolerance against PE developed after 21 days of consecutive daily injections or the fourth week of PE administration. Compared with a single administration, it was observed that the tolerant rats had a lower rate of PE clearance from the blood, which was independent of the stress response. In addition, weekly PE injections caused injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy group (–OCH3) of PEG, failed to respond to the PEs with a different terminal group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by PE, regardless of the mode of administration. Further study of this mechanism suggested that monocytes play an essential role in the suppression of innate immunity. These findings provide novel insights into the understanding of the innate immune system.
doi:10.2147/IJN.S66318
PMCID: PMC4128795  PMID: 25120362
immunologic tolerance; innate immune system; pharmacokinetics; biodistribution; antigenic specificity
12.  Oral Immunization with Escherichia coli Expressing a Lipidated Form of LigA Protects Hamsters against Challenge with Leptospira interrogans Serovar Copenhageni 
Infection and Immunity  2014;82(2):893-902.
Leptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine. Leptospira interrogans serovar Copenhageni transmitted from Rattus norvegicus to humans is the most prevalent cause of urban leptospirosis. We examined L. interrogans LigA, domains 7 to 13 (LigA7-13), as an oral vaccine delivered by Escherichia coli as a lipidated, membrane-associated protein. The efficacy of the vaccine was evaluated in a susceptible hamster model in terms of the humoral immune response and survival from leptospiral challenge. Four weeks of oral administration of live E. coli expressing LigA7-13 improved survival from intraperitoneal (i.p.) and intradermal (i.d.) challenge by L. interrogans serovar Copenhageni strain Fiocruz L1-130 in Golden Syrian hamsters. Immunization with E. coli expressing LigA7-13 resulted in a systemic antibody response, and a significant LigA7-13 IgG level after the first 2 weeks of immunization was completely predictive of survival 28 days after challenge. As in previous LigA vaccine studies, all immunized hamsters that survived infection had renal leptospiral colonization and histopathological changes. In summary, an oral LigA-based vaccine improved survival from leptospiral challenge by either the i.p. or i.d. route.
doi:10.1128/IAI.01533-13
PMCID: PMC3911400  PMID: 24478102
13.  Cooperation with both synergistic and local interactions can be worse than each alone 
Scientific Reports  2014;4:5536.
Cooperation is ubiquitous ranging from multicellular organisms to human societies. Population structures indicating individuals' limited interaction ranges are crucial to understand this issue. But it remains unknown to what extend multiple interactions involving nonlinearity in payoff influence the cooperation in structured populations. Here we show a rule, which determines the emergence and stabilization of cooperation, under multiple discounted, linear, and synergistic interactions. The rule is validated by simulations in homogenous and heterogenous structured populations. We find that the more neighbours there are the harder for cooperation to evolve for multiple interactions with linearity and discounting. For synergistic scenario, however, distinct from its pairwise counterpart, moderate number of neighbours can be the worst, indicating that synergistic interactions work with strangers but not with neighbours. Our results suggest that the combination of different factors which promotes cooperation alone can be worse than that with every single factor.
doi:10.1038/srep05536
PMCID: PMC4078301  PMID: 24985887
14.  Penicillium fusisporum and P. zhuangii, Two New Monoverticillate Species with Apical-Swelling Stipes of Section Aspergilloides Isolated from Plant Leaves in China 
PLoS ONE  2014;9(7):e101454.
Two new Penicillium species isolated from plant leaves are reported here, namely, P. fusisporum (type strain AS3.15338T = NRRL 62805T = CBS 137463T) and P. zhuangii (type strain AS3.15341T = NRRL 62806T = CBS 137464T). P. fusisporum is characterized by fast growth rate, apical-swelling monoverticillate penicilli, verrucose stipes, fusiform to oblong conidia about 3.5–4×2–2.5 µm and cinnamon-colored sclerotia. While P. zhuangii presents a moderate growth rate, it also bears apical-swelling monoverticillate penicilli but its stipes are smooth-walled, and produces ovoid to globose smooth-walled conidia about 3–3.5 µm. Both species belong to section Aspergilloides, and P. fusisporum is related to “P. thomii var. flavescens”, while P. zhuangii is morphologically similar to P. lividum. Phylogenetic analyses of sequences of calmodulin and beta-tubulin genes both show that the two new taxa form distinct monophyletic clades.
doi:10.1371/journal.pone.0101454
PMCID: PMC4079715  PMID: 24988489
15.  Bluffing promotes overconfidence on social networks 
Scientific Reports  2014;4:5491.
The overconfidence, a well-established bias, in fact leads to unrealistic expectations or faulty assessment. So it remains puzzling why such psychology of self-deception is stabilized in human society. To investigate this problem, we draw lessons from evolutionary game theory which provides a theoretical framework to address the subtleties of cooperation among selfish individuals. Here we propose a spatial resource competition model showing that, counter-intuitively, moderate values rather than large values of resource-to-cost ratio boost overconfidence level most effectively. In contrast to theoretical results in infinite well-mixed populations, network plays a role both as a “catalyst” and a “depressant” in the spreading of overconfidence, especially when resource-to-cost ratio is in a certain range. Moreover, when bluffing is taken into consideration, overconfidence evolves to a higher level to counteract its detrimental effect, which may well explain the prosperity of this “erroneous” psychology.
doi:10.1038/srep05491
PMCID: PMC4074791  PMID: 24974793
16.  Dose-Dependent Effect of Estrogen Suppresses the Osteo-Adipogenic Transdifferentiation of Osteoblasts via Canonical Wnt Signaling Pathway 
PLoS ONE  2014;9(6):e99137.
Fat infiltration within marrow cavity is one of multitudinous features of estrogen deficiency, which leads to a decline in bone formation functionality. The origin of this fat is unclear, but one possibility is that it is derived from osteoblasts, which transdifferentiate into adipocytes that produce bone marrow fat. We examined the dose-dependent effect of 17β-estradiol on the ability of MC3T3-E1 cells and murine bone marrow-derived mesenchymal stem cell (BMMSC)-derived osteoblasts to undergo osteo-adipogenic transdifferentiation. We found that 17β-estradiol significantly increased alkaline phosphatase activity (P<0.05); calcium deposition; and Alp, Col1a1, Runx2, and Ocn expression levels dose-dependently. By contrast, 17β-estradiol significantly decreased the number and size of lipid droplets, and Fabp4 and PPARγ expression levels during osteo-adipogenic transdifferentiation (P<0.05). Moreover, the expression levels of brown adipocyte markers (Myf5, Elovl3, and Cidea) and undifferentiated adipocyte markers (Dlk1, Gata2, and Wnt10b) were also affected by 17β-estradiol during osteo-adipogenic transdifferentiation. Western blotting and immunostaining further showed that canonical Wnt signaling can be activated by estrogen to exert its inhibitory effect of osteo-adipogenesis. This is the first study to demonstrate the dose-dependent effect of 17β-estradiol on the osteo-adipogenic transdifferentiation of MC3T3-E1 cells and BMMSCs likely via canonical Wnt signaling. In summary, our results indicate that osteo-adipogenic transdifferentiation modulated by canonical Wnt signaling pathway in bone metabolism may be a new explanation for the gradually increased bone marrow fat in estrogen-inefficient condition.
doi:10.1371/journal.pone.0099137
PMCID: PMC4053448  PMID: 24918446
17.  Aspiration-Based Partner Switching Boosts Cooperation in Social Dilemmas 
PLoS ONE  2014;9(6):e97866.
Most previous studies concerning linking dynamics often assumed that links pairing individuals should be identified and treated differently during topology adjusting procedure, in order to promote cooperation. A common assumption was that cooperators were expected to avoid being exploited by quickly breaking up relationships with defectors. Then the so-called prosocial links linking two cooperators (abbreviated as CC links hereafter) would be much favored by evolution, whereby cooperation was promoted. However, we suggest that this is not always necessary. Here, we developed a minimal model in which an aspiration-based partner switching mechanism was embedded to regulate the evolution of cooperation in social dilemmas. Individuals adjusted social ties in a self-questioning manner in line with the learning theory. Less game information was involved during dynamic linking and all links were tackled anonymously irrespective of their types (i.e., CD links, DD links, or CC links). The main results indicate that cooperation flourishes for a broad range of parameters. The denser the underlying network, the more difficult the evolution of cooperation. More importantly, moderate aspirations do much better in promoting the evolution of altruistic behavior and for most cases there exists the optimal aspiration level that most benefits cooperation. Too strong or too weak selection intensity turns out to be pretty conducive to the evolution of cooperation in such a dynamical system.
doi:10.1371/journal.pone.0097866
PMCID: PMC4045582  PMID: 24896269
18.  Development and Validation of an Animal Model of Prostate Inflammation-Induced Chronic Pelvic Pain: Evaluating from Inflammation of the Prostate to Pain Behavioral Modifications 
PLoS ONE  2014;9(5):e96824.
Background
Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan.
Methods
Male Sprague-Dawley rats weighing 250–350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7d, 14d and 30d of injection), radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX) 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan.
Results
Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 24 h and 7d(p = 0.022,0.046, respectively), and a significant reduction in heat threshold (thermal hyperalgesia) at 24 h, 7d and 14d(p = 0.014, 0.018, 0.002, respectively) in the scrotal skin. Significant increase of inflammatory cell accumulation,COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14d after injection.
Conclusions
Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.
doi:10.1371/journal.pone.0096824
PMCID: PMC4019557  PMID: 24823660
19.  Random allocation of pies promotes the evolution of fairness in the Ultimatum Game 
Scientific Reports  2014;4:4534.
In the Ultimatum Game, two players are offered a chance to win a pie. The proposer suggests how to split the pie. The responder can either accept or reject the deal. If an agreement is not reached, neither player gets anything. Both game theory and evolutionary game theory predict the rational solution that the proposer offers the smallest possible share and the responder accepts it. Fairness thus requires additional mechanisms for natural selection to favor it. Studies to date assumed that individuals have competed for the fixed size of pies, in sharp contrast with real situations, where randomness is ubiquitous. Here we study the impact of random allocation of pies on the evolution of fairness in the Ultimatum Game. Interestingly, we find that the evolution of fairness can be promoted by the randomness associated with the size of pies, without the support of any additional evolutionary mechanisms.
doi:10.1038/srep04534
PMCID: PMC3971395  PMID: 24686840
20.  Optical properties of Ag nanoparticle-polymer composite film based on two-dimensional Au nanoparticle array film 
Nanoscale Research Letters  2014;9(1):155.
The nanocomposite polyvinyl pyrrolidone (PVP) films containing Ag nanoparticles and Rhodamine 6G are prepared on the two-dimensional distinctive continuous ultrathin gold nanofilms. We investigate the optical properties and the fluorescence properties of silver nanoparticles-PVP polymer composite films influenced by Ag nanoparticles and Au nanoparticles. Absorption spectral analysis suggests that the prominently light absorption in Ag nanowire/PVP and Ag nanowire/PVP/Au film arises from the localized surface plasmon resonance of Ag nanowire and Au nanofilm. The enhanced fluorescence is observed in the presence of Ag nanowire and Au nanofilm, which is attributed to the excitation of surface plasmon polariton resonance of Ag nanowire and Au nanofilm. The gold nanofilm is proven to be very effective fluorescence resonance energy transfer donors. The fabricated novel structure, gold ultrathin continuous nanofilm, possesses high surface plasmon resonance properties and prominent fluorescence enhancement effect. Therefore, the ultrathin continuous gold nanofilm is an active substrate on nanoparticle-enhanced fluorescence.
doi:10.1186/1556-276X-9-155
PMCID: PMC3974418  PMID: 24685186
Metal nanocomposite; Optical properties; Localized surface plasmon resonance; Surface plasmon-enhanced fluorescence
21.  A historically-controlled Phase III study in adults to characterize the acceptability of a process change for manufacturing inactivated quadrivalent influenza vaccine 
BMC Infectious Diseases  2014;14:133.
Background
An inactivated quadrivalent influenza vaccine (QIV) was recently licenced in the US as a thimerosal-free formulation presented in a pre-filled syringe. A multidose presentation is preferred in some settings due to reduced acquisition and cold storage costs. We assessed the immunogenicity and safety of a thimerosal-containing QIV formulated using a new manufacturing process for presentation in multidose vials.
Methods
Two Phase III non-randomized studies separately evaluated inactivated trivalent influenza vaccine (TIV; 2010–2011; historical control) and a QIV (2011–2012). The QIV contained the same strains as the TIV plus an additional B strain. Both vaccines contained thimerosal to allow multidose presentation: this preservative was added to the QIV during the final formulation step using a new process, whereas it was added to the TIV early in the manufacturing process using an established method. The TIV study included 50 and 70 subjects aged 18–60 and >60 years, respectively; the QIV study included 56 subjects in each age stratum. Immunogenicity was assessed using hemagglutination-inhibition (HI) assays. Reactogenicity was assessed during the 4-day post-vaccination periods and unsolicited adverse events (AEs) were assessed during the 21-day post-vaccination periods.
Results
The TIV and QIV were immunogenic in both age strata. With the QIV and TIV respectively, the seroconversion rates were 48.2–62.7% and 71.4–83.7% for influenza A, and 33.9–62.5% and 67.3–72.9% for influenza B. With the QIV and TIV respectively, the seroprotection rates were 92.9–98.2% and 98.2–100% for influenza A, and 88.6–100% and 95.9–98.6% for influenza B. Pre-vaccination titers were higher in the QIV versus TIV study which confounds a direct comparison and likely explains the lower seroconversion rates observed in the QIV study. There were no safety concerns raised with TIV or QIV.
Conclusions
The thimerosal-containing QIV formulated using a new process was immunogenic, conforming to regulatory acceptance criteria, with a reactogenicity and safety profile in line with the TIV manufactured using a licensed process. These results support acceptability of a manufacturing process change in which the thimerosal preservative is added at the point at which batches are filled into multidose vials.
Trial registration
These trials were registered at ClinicalTrials.gov: NCT01440387; NCT01153685.
doi:10.1186/1471-2334-14-133
PMCID: PMC3995899  PMID: 24606983
Thimerosal-containing; Quadrivalent; Trivalent; Inactivated; Influenza; Adults
22.  Dissociation of the H3K36 demethylase Rph1 from chromatin mediates derepression of environmental stress-response genes under genotoxic stress in Saccharomyces cerevisiae 
Molecular Biology of the Cell  2013;24(20):3251-3262.
The H3K36 demethylase Rph1 is a transcriptional repressor for stress-responsive genes in yeast. Rph1-mediated transcriptional repression is relieved by phosphorylation of Rph1, reduced Rph1 level, and dissociation of Rph1 from chromatin with genotoxic stress. Rph1 may function as a regulatory node in different stress-signaling pathways.
Cells respond to environmental signals by altering gene expression through transcription factors. Rph1 is a histone demethylase containing a Jumonji C (JmjC) domain and belongs to the C2H2 zinc-finger protein family. Here we investigate the regulatory network of Rph1 in yeast by expression microarray analysis. More than 75% of Rph1-regulated genes showed increased expression in the rph1-deletion mutant, suggesting that Rph1 is mainly a transcriptional repressor. The binding motif 5′-CCCCTWA-3′, which resembles the stress response element, is overrepresented in the promoters of Rph1-repressed genes. A significant proportion of Rph1-regulated genes respond to DNA damage and environmental stress. Rph1 is a labile protein, and Rad53 negatively modulates Rph1 protein level. We find that the JmjN domain is important in maintaining protein stability and the repressive effect of Rph1. Rph1 is directly associated with the promoter region of targeted genes and dissociated from chromatin before transcriptional derepression on DNA damage and oxidative stress. Of interest, the master stress-activated regulator Msn2 also regulates a subset of Rph1-repressed genes under oxidative stress. Our findings confirm the regulatory role of Rph1 as a transcriptional repressor and reveal that Rph1 might be a regulatory node connecting different signaling pathways responding to environmental stresses.
doi:10.1091/mbc.E12-11-0820
PMCID: PMC3806659  PMID: 23985319
23.  Supramolecular Luminescence from Oligofluorenol-Based Supramolecular Polymer Semiconductors 
Supramolecular luminescence stems from non-covalent exciton behaviors of active π-segments in supramolecular entities or aggregates via intermolecular forces. Herein, a π-conjugated oligofluorenol, containing self-complementary double hydrogen bonds, was synthesized using Suzuki coupling as a supramolecular semiconductor. Terfluorenol-based random supramolecular polymers were confirmed via concentration-dependent nuclear magnetic resonance (NMR) and dynamic light scattering (DLS). The photoluminescent spectra of the TFOH-1 solution exhibit a green emission band (g-band) at approximately ~520 nm with reversible features, as confirmed through titration experiments. Supramolecular luminescence of TFOH-1 thin films serves as robust evidence for the aggregates of g-band. Our results suggest that the presence of polyfluorene ketone defects is a sufficient condition, rather than a sufficient-necessary condition for the g-band. Supramolecular electroluminescence will push organic devices into the fields of supramolecular optoelectronics, spintronics, and mechatronics.
doi:10.3390/ijms141122368
PMCID: PMC3856068  PMID: 24232455
luminescence; supramolecular polymers; polyfluorenes; hydrogen bonds; thin films
24.  MicroRNA-26a Inhibits Angiogenesis by Down-Regulating VEGFA through the PIK3C2α/Akt/HIF-1α Pathway in Hepatocellular Carcinoma 
PLoS ONE  2013;8(10):e77957.
Background & Aims
microRNAs (miRNAs) have been reported to regulate angiogenesis by down-regulating the expression of pro-angiogenic or anti-angiogenic factors. The aims of this study were to investigate whether miR-26a inhibited angiogenesis by down-regulating vascular endothelial growth factor A (VEGFA) and its clinical relevance in hepatocellular carcinoma (HCC).
Methods
The expression of miR-26a was modified in HepG2 and HCCLM3 cell lines respectively, and a panel of angiogenic factors was measured by real-time PCR in the cells. A luciferase reporter assay was used to validate the target gene of miR-26a. Specific inhibitors of signal transduction pathway and siRNA approaches were used to explore the regulatory mechanism of miR-26a. Migration and tube forming assays were conducted to show the changes of angiogenesis induced by miR-26a and its target genes. Finally animal studies were used to further validate those findings.
Results
Ectopic expression of miR-26a exhibited decreased levels of VEGFA in HepG2 cells. Migration and tube forming of human umbilical vein endothelial cells (HUVECs) were decreased in the conditioned medium from ectopic expression of miR-26a in HepG2 cells compared to control HepG2 cells. The pro-angiogenic effects of the conditioned medium of HepG2 cells on HUVECs were specifically decreased by LY294002, YC-1, and bevacizumab. Integrated analysis disclosed PIK3C2α as a downstream target gene of miR-26a. Ectopic expression of miR-26a suppressed ectopic and orthotopic tumor growth and vascularity in nude mice. The results in HCCLM3 were consistent with those in HepG2. miR-26a expression was inversely correlated with VEGFA expression in HCC patients.
Conclusions
miR-26a modulated angiogenesis of HCC through the PIK3C2α/Akt/HIF-1α/VEGFA pathway. The expression of VEGFA was inversely correlated with miR-26a expression in HCC tumors.
doi:10.1371/journal.pone.0077957
PMCID: PMC3806796  PMID: 24194905
25.  Medium-term Outcomes of Cemented Prostheses and Cementless Modular Prostheses in Revision Total Hip Arthroplasty 
Scientific Reports  2013;3:2796.
There is an increasing trend towards cementless modular femoral prostheses for revision hip replacement surgery, especially in patients with severe proximal femoral bone defects. However, for minor femoral bone defects, the benefit of cementless modular is not clear. We designed a retrospective cross-sectional study to compare outcomes of the two femoral implant designs. There were no significant differences in terms of visual analog pain scores, Harris hip scores, femoral bone restoration, stem subsidence, leg length correction, or overall complication rate. Three femoral reoperations (11%) occurred in the cemented group, and two (9%) in the cementless modular group. One femoral stem re-revised (4%) in the cemented group due to recurrent deep infection. Five-year survival for femoral reoperation was 88.2% for patients with the cemented implant and 91.3% for cementless group. Both groups had good clinical and radiological outcomes for femoral revision in patients with minor femoral bone defects during medium-term follow-up.
doi:10.1038/srep02796
PMCID: PMC3786300  PMID: 24077449

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